A model to explain how starvation for different nutrients regulates RpoS by different mechanisms. The rpoS mRNA is translated at low levels due to its 5′ untranslated region forming a hairpin structure and occluding the Shine-Dalgarno sequence. Translation of the message is significantly enhanced in an Hfq-dependent manner in response to perceived phosphorus limitation, presumably by binding of a heretofore-uncharacterized small RNA. This causes significant increase in RpoS protein levels, though the protein is not as stable as it is under carbon starvation. Carbon starvation inhibits SprE (RssB)-mediated degradation of RpoS through the ClpXP protease. This leads to accumulation of highly stable RpoS protein. Nitrogen starvation shows only a modest increase in RpoS levels during starvation, so it is expected that its primary effect on RpoS regulation is at the level of activity, since RpoS plays an important role under nitrogen starvation. By influencing different elements of the pathway, each starvation signal activates RpoS regardless of the status—starvation level or excess—of the other nutrients. Thus, the signals act independently and do not interfere with each other.